The goal of this project is to improve our understanding of carcinogenesis in gynecological cancers and to improve definition of the morphological criteria and biological behavior. During the past year, the nuclear DNA findings of gynecologic neoplasms were compared with the morphometric measurements based on the routine histologic sections. Of the 16 in situ adenocarcinomas of the uterine cervix analyzed, all but one had an aneuploid DNA distribution, indicating that the great majority of these lesions were neoplastic with potential of progressing into invasive adenocarcinoma. By morphometry, the nuclear size was the most effective means of separating these precursors from benign simulators such as microglandular hyperplasia and chronic endocervicitis. The mean nuclear area for in situ adenocarcinoma was 63.1+16.0 sq. microns as compared to 39.0+7.0 sq. microns for microglandular hyperplasia and 40.8+7.0 sq. microns for chronic endocervicitis. In patients with invasive cervical adenocarcinoma, the clinical stage and the ploidy level of stem cell lines were the most significant prognostic factors. Twenty-five percent of patients with clinical stage I-II, low ploidy tumors (stem cell modal value less than triploid) developed recurrence or died of tumor as compared to 75% for those with higher ploidy tumors of similar clinical stage (P less than 0.05). The nuclear size of tumor cells as determined by morphometry was found to be a more reliable prognosticator than the histologic grade. Sixty-four percent of patients with mean nuclear area of tumor cells greater than 53 sq. microns had recurrence or died of tumor as compared to 25% for those with smaller mean nuclear area (clinical stage I-II, P less than 0.05). In borderline malignant serous tumors of the ovary, 80% of tumors with aneuploid DNA pattern recurred after surgical resection in contrast to 18% recurrence rate for diploid tumors. Among the patients with similar tumor type and comparable clinical stage, these quantitative analyses have identified a subpopulation with a poor prognosis. (3)